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Abstract Decreased blood‐tissue oxygenation at high altitude (HA) increases mitochondrial oxidant production and reduces exercise capacity. 5‐Hydroxymethylfurfural (5‐HMF) is an antioxidant that increases hemoglobin's binding affinity for oxygen. For these reasons, we hypothesized that 5‐HMF would improve muscle performance in rats exposed to a simulated HA of ~5500 m. A secondary objective was to measure mitochondrial activity and dynamic regulation of fission and fusion because they are linked processes impacted by HA. Fisher 344 rats received 5‐HMF (40 mg/kg/day) or vehicle during exposure to sea level or HA for 72 h. Right ankle plantarflexor muscle function was measured pre‐ and post‐exposure. Post‐exposure measurements included arterial blood gas and complete blood count, flexor digitorum brevis myofiber superoxide production and mitochondrial membrane potential (ΔΨm), and mitochondrial dynamic regulation in the soleus muscle. HA reduced blood oxygenation, increased superoxide levels and lowered ΔΨm, responses that were accompanied by decreased peak isometric torque and force production at frequencies >75 Hz. 5‐HMF increased isometric force production and lowered oxidant production at sea level. In HA exposed animals, 5‐HMF prevented a decline in isometric force production at 75–125 Hz, prevented an increase in superoxide levels, further decreased ΔΨm, and increased mitochondrial fusion 2 protein expression. These results suggest that 5‐HMF may prevent a decrease in hypoxic force production during submaximal isometric contractions by an antioxidant mechanism.

Background Significant reductions in ambient pressure subject an individual to risk of decompression illness (DCI); with incidence up to 35 per 10,000 dives. In severe cases, the central nervous system is often compromised (>80%), making DCI among the most morbid of diving related injuries. While hyperbaric specialists suggest initiating recompression therapy with either a Treatment Table 6 (TT6) or 6A (TT6A), the optimal initial recompression treatment for severe DCI is unknown. Methods Swine were exposed to an insult dive breathing air at 7.06 ATA (715.35 kPa) for 24 min followed by rapid decompression at a rate of 1.82 ATA/min (184.41 kPa/min). Swine that developed neurologic DCI within 1 hour of surfacing were block randomized to one of four United States Navy Treatment Tables (USN TT): TT6, TT6A-air (21% oxygen, 79% nitrogen), TT6A-nitrox (50% oxygen, 50% nitrogen), and TT6A-heliox (50% oxygen, 50% helium). The primary outcome was the mean number of spinal cord lesions, which was analyzed following cord harvest 24 hours after successful recompression treatment. Secondary outcomes included spinal cord lesion incidence and gross neurologic outcomes based on a pre- and post- modified Tarlov assessment. We compared outcomes among these four groups and between the two treatment profiles (i.e. TT6 and TT6A). Results One-hundred and forty-one swine underwent the insult dive, with 61 swine meeting inclusion criteria (43%). We found no differences in baseline characteristics among the groups. We found no significant differences in functional neurologic outcomes (p = 0.77 and 0.33), spinal cord lesion incidence (p = 0.09 and 0.07), or spinal cord lesion area (p = 0.51 and 0.17) among the four treatment groups or between the two treatment profiles, respectively. While the trends were not statistically significant, animals treated with TT6 had the lowest rates of functional deficits and the fewest spinal cord lesions. Moreover, across all animals, functional neurologic deficit had strong correlation with lesion area pathology (Logistic Regression, p < 0.01, Somers’ D = 0.74). Conclusions TT6 performed as well as the other treatment tables and is the least resource intensive. TT6 is the most appropriate initial treatment for neurologic DCI in swine, among the tables that we compared.

Introduction:The consequences of low partial pressure of O2 include low arterial O2 saturations (SaO2), low blood O2 content (CaO2), elevated mean pulmonary artery pressure (PAP), and decreased O2 consumption VO2. 5-hydroxymethyl-2-furfural (5-HMF) binds to the N-terminal valine of hemoglobin (HgB) and increases its affinity to O2. We used an instrumented, sedated swine model to study the effect of 5-HMF on cardiovascular parameters during exposure to acute normobaric hypoxia (NH).MethodsTwenty-three sedated and instrumented swine were randomly assigned to one of three treatment groups and received equal volume of normal saline (VEH), 20 mg/kg 5-HMF (5-HMF-20) or 40 mg/kg 5-HMF (5-HMF-40). Animals then breathed 10% FiO2 for 120 min. Parameters recorded were Cardiac Output (CO), Mean Arterial Blood Pressure (MAP), Heart Rate (HR), Mean Pulmonary Artery Pressure (PAP), SaO2 and saturation of mixed venous blood (SvO2). The P50 was measured at fixed time intervals prior to and during NH.Results5-HMF decreased P50. In the first 30 min of NH, treatment with 5-HMF-20 and 5-HMF-40 resulted in a (1) significantly smaller decrement in SaO2 and SvO2, (2) significantly lower HR and CO, and (3) smaller increase in PAP compared to VEH. In the 120 min of NH there was a trend toward improved mortality with 5-HMF treatment.Conclusion5-HMF treatment decreased P50, improved SaO2, and mitigated increases in PAP in this swine model of NH.

BackgroundSignificant reductions in ambient pressure subject an individual to risk of decompression illness (DCI); with incidence up to 35 per 10,000 dives. In severe cases, the central nervous system is often compromised (>80%), making DCI among the most morbid of diving related injuries. While hyperbaric specialists suggest initiating recompression therapy with either a Treatment Table 6 (TT6) or 6A (TT6A), the optimal initial recompression treatment for severe DCI is unknown.MethodsSwine were exposed to an insult dive breathing air at 7.06 ATA (715.35 kPa) for 24 min followed by rapid decompression at a rate of 1.82 ATA/min (184.41 kPa/min). Swine that developed neurologic DCI within 1 hour of surfacing were block randomized to one of four United States Navy Treatment Tables (USN TT): TT6, TT6A-air (21% oxygen, 79% nitrogen), TT6A-nitrox (50% oxygen, 50% nitrogen), and TT6A-heliox (50% oxygen, 50% helium). The primary outcome was the mean number of spinal cord lesions, which was analyzed following cord harvest 24 hours after successful recompression treatment. Secondary outcomes included spinal cord lesion incidence and gross neurologic outcomes based on a pre- and post- modified Tarlov assessment. We compared outcomes among these four groups and between the two treatment profiles (i.e. TT6 and TT6A).ResultsOne-hundred and forty-one swine underwent the insult dive, with 61 swine meeting inclusion criteria (43%). We found no differences in baseline characteristics among the groups. We found no significant differences in functional neurologic outcomes (p = 0.77 and 0.33), spinal cord lesion incidence (p = 0.09 and 0.07), or spinal cord lesion area (p = 0.51 and 0.17) among the four treatment groups or between the two treatment profiles, respectively. While the trends were not statistically significant, animals treated with TT6 had the lowest rates of functional deficits and the fewest spinal cord lesions. Moreover, across all animals, functional neurologic deficit had strong correlation with lesion area pathology (Logistic Regression, p < 0.01, Somers' D = 0.74).ConclusionsTT6 performed as well as the other treatment tables and is the least resource intensive. TT6 is the most appropriate initial treatment for neurologic DCI in swine, among the tables that we compared.